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Synthesis 2025; 57(12): 1941-1954
DOI: 10.1055/a-2550-7239
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Total Synthesis of Anticancer Pacharin, Bauhiniastatin 4, and Bauhinoxepins C and D

Pattarapon Sang-aroon‡
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Norasian Boosaman‡
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Intouch Rakchaya‡
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Wiradet Siri
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Asamaporn Tieojaroenkit
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Nutthawat Chuanopparat 
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Paiboon Ngernmeesri  ∗
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
› Author Affiliations
Financial support was provided by the National Research Council of Thailand (NRCT5-RSA63002-10), the Kasetsart University Research and Development Institute (KURDI), the Center of Excellence for Innovation in Chemistry (PERCH-CIC), Ministry of Higher Education, Science, Research and Innovation, the Thailand Toray Science Foundation (TTSF), and the Department of Chemistry and the Faculty of Science, Kasetsart University.
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Abstract

Reported herein is the total synthesis of anticancer pacharin, bauhiniastatin 4, and bauhinoxepins C and D. The synthetic strategy features a cascade reaction involving intermolecular nucleophilic aromatic substitution followed by intramolecular Knoevenagel condensation to form a dibenzo[b,f]oxepine scaffold of these compounds. Pacharin and bauhiniastatin 4 were synthesized in eight steps from 2-methylresorcinol with overall yields of 5.4% and 8.3%, respectively. Similarly, bauhinoxepins C and D were synthesized in seven steps with overall yields of 3.5% and 2.6%, respectively. This methodology offers an efficient route for accessing these natural products with implications for medicinal and synthetic chemistry.

Key words

natural product synthesis - cascade reaction - dibenzo[b,f]oxepines - anticancer agents - nucleophilic aromatic substitution - Knoevenagel condensation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2550-7239.
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Publication History

Received: 04 February 2025

Accepted after revision: 04 March 2025

Accepted Manuscript online:
04 March 2025

Article published online:
07 April 2025

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